Category Archives: Stem Cells

Newswise UCLA researchers have discovered a type of cell that is the missing link between bone marrow stem cells and all the cells of the human immune system, a finding that will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function.

The studies were done using human bone marrow, which contains all the stem cells that produce blood during postnatal life.

We felt it was especially important to do these studies using human bone marrow as most research into the development of the immune system has used mouse bone marrow, said study senior author Dr. Gay Crooks, co-director of the Eli and Edythe Broad Center of Regenerative Medicine and a co-director of the Cancer and Stem Cell Biology program at UCLAs Jonsson Comprehensive Cancer Center. The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of postnatal life.

The research team was intrigued to find this particular bone marrow cell because it opens up a lot of new possibilities in terms of understanding how human immunity is produced from stem cells throughout life, said Crooks, a professor of pathology and pediatrics.

Understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemias, or cancers of the blood.

The study appears Sept. 2 in the early online edition of Nature Immunology.

Before this study, researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce intermediate stages of development called progenitors, which make various blood lineages like red blood cells or platelets. Crooks was most interested in the creation of the progenitors that form the entire immune system, which consists of many different cells called lymphocytes, each with a specialized function to fight infection.

Like the stem cells, the progenitor cells are also very rare, so before we can study them we needed to find the needle in the haystack. said Lisa Kohn, a member of the UCLA Medical Scientist Training Program and first author in the paper.

Previous work had found a fairly mature type of lymphocyte progenitor with a limited ability to differentiate, but the new work describes a more primitive type of progenitor primed to produce the entire immune system, Kohn said

Once the lymphoid primed progenitor had been identified, Crooks and her team studied how gene expression changed during the earliest stages of its production from stem cells.

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UCLA Researchers Discover "Missing Link" Between Stem Cells and the Immune System

The molecular circuitry controlling asymmetric cell division in roots resembles a flip-flop switch.

(Phys.org)For organisms to grow and develop, they must produce tissues with distinct functions, each one made up of similar cells. These different tissues are derived from stem cells. How stem cells divide to create new cell types is known as asymmetric cell division, and is obviously crucial to the overall development of the organism. In plants, whose cells cannot migrate, the location where a stem cell undergoes asymmetric cell division must also be crucial to ensuring tissues develop in the correct place.

In research published in the journal Cell, a collaboration between theoretical biologists and experimentalists, headed by Stan Mare of the John Innes Centre, and Ben Scheres, of the University of Utrecht, the Netherlands, uncovered a molecular switch that integrates signals to ensure these asymmetric cell divisions happen in the right place and at the right time, to produce layers of specialised tissue in the root.

"Through an experimental-modelling cycle, we have unravelled how stem cells in the Arabidopsis root regulate asymmetric cell divisions that give rise to two new cell identities at the correct position," said Dr Stan Mare of the John Innes Centre, which is strategically funded by the Biotechnology and Biological Sciences Research Council. "We dissected the underlying molecular circuit which operates in each cell, and found that it presented a highly robust bistable behaviour, due to two positive feedback loops involving the proteins SHR, SCR and the cell-cycle related players RBR and CYCLD6;1. In other words, we showed that the circuit behaves like a switch."

Bistable systems, which can only exist in one of two states, are found in nature where tight control is needed. Positive feedback loops are common features of them as they help make the rapid switch from one state to another.

Having identified this switch, the next step was to work out how the plant turns it on and off, so that only the correct stem cells perform asymmetric division, and in the right location for the overall development of the plant.

To do this, Dr Stan Mare together with Dr Vernica Grieneisen constructed a mathematical model, an in silico version of the root and the molecular circuitry behind the switch.

The physical location of an asymmetric cell division relies on the interaction of the plant hormone auxin and the protein SHR. Previous work by Dr Grieneisen had shown how auxin accumulates in the root tip through a reflux-loop mechanism established by polarly localized auxin efflux carriers in cells, and that the concentration of auxin declines the further from the root tip, forming a gradient with its highest peak at the stem cells.SHR protein sets up a similar gradient, but perpendicular to the auxin gradient, radiating out.

"We found that the cells that undergo these special cell divisions are located right at the crossroads of these two gradients," said Dr Grieneisen.

The cell divisions also trigger protein degradation, which turns the switch off again. This is needed to prevent uncontrolled development.

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'Flip-flop' switch discovered behind key cellular process

Stem Cells Inc, (STEM), developer of stem cell-based treatments for spinal injury, is up for the second day in a row Friday in pre-market trading, after it closed Thursday at $1.96, a 19% gain on the day. The gains came after the company announced that it will be presenting data from its Phase I/II clinical trial on Monday, Sept. 3 at the International Spinal Cord Society and will hold a conference call the following day. Trading volume Thursday was three times its 3-month average. The presentation will include interim data from the study`s first cohort, which has three partially paralyzed patients being treated with STEM`s proprietary HuCNS-SC cells. Researchers are looking for efficacy - measured by improvement in motor function, sensation, and bladder control - and safety in the first of three planned cohorts, each with more mild paralysis than the previous. Share price is likely to remain strong on Friday and into the meeting, as most analysts expect some positive results from the trial. If Monday`s data looks good for STEM, shares may climb higher on momentum, however, negative results will have disastrous effects on the stock. STEM is up 140% in 2012.

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PropThink: STEM Gains on Anticipation of Interim Trial Data to be Presented Monday

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

Verastem, Inc., (VSTM) a biopharmaceutical company focused on discovering and developing drugs to treat breast and other cancers by targeting cancer stem cells, announced presentations at several upcoming investment conferences. The presentation details are as follows:

A webcast of each presentation can be accessed by visiting the investors section of the Companys website at http://www.verastem.com. A replay of the webcast will be archived on the Verastem website for two weeks following the presentation date.

About Verastem, Inc.

Verastem, Inc. (VSTM) is a biopharmaceutical company focused on discovering and developing drugs to treat breast and other cancers by targeting cancer stem cells. Cancer stem cells are an underlying cause of tumor recurrence and metastasis. For more information please visit http://www.verastem.com.

Forward-looking statements:

Any statements in this press release about future expectations, plans and prospects for the Company constitute forward-looking statements.Actual results may differ materially from those indicated by such forward-looking statements. The Company anticipates that subsequent events and developments will cause the Companys views to change.However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.

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Verastem to Present at Upcoming Investor Conferences

Stem cell-powered implant set to revolutionise orthopaedic surgery

Scientists at the University of Glasgow are working to harness the regenerative power of stem cells to improve orthopaedic implant surgery. They are collaborating with surgeons at Glasgows Southern General Hospital to develop a new type of orthopaedic implant which could be considerably stronger and more long-lived than the current generation of products.

Currently, implants are commonly made from materials such as polyethylene, stainless steel, titanium or ceramic and have a limited lifespan due to loosening, requiring replacement after 15 or 20 years of use. In hip replacement surgery, the head of the thigh bone is removed and replaced with an implant which is held in place by a rod fixed inside the marrow along the length of the bone.

Marrow is a rich source of mesenchymal stem cells, which have the potential to divide, or differentiate, into other types of cells such as skin, muscle or bone which can improve the process of healing. However, stem cells can also differentiate into cells which have no use in therapy. Artificially controlling the final outcome to ensure the desired type of cells are created is very difficult, even under laboratory conditions.

When traditional implants are fixed into bone marrow, the marrows stem cells do not receive messages from the body to differentiate into bone cells, which would help create a stronger bond between the implant and the bone. Instead, they usually differentiate into a buildup of soft tissue which, combined with the natural loss of bone density which occurs as people age, can weaken the bond between the implant and the body.

The team from the University of Glasgows Colleges of Science and Engineering and Medical, Veterinary and Life Sciences have found a reliable method to encourage bone cell growth around a new type of implant. The implant will be made of an advanced implantable polymer known as PEEK-OPTIMA, from Invibio Biomaterial Solutions, which is already commonly used in spinal and other orthopaedic procedures.

Dr Matthew Dalby, of the Universitys Institute of Molecular, Cell and Systems Biology, explained: Last year, we developed a plastic surface which allowed a level of control over stem cell differentiation which was previously impossible. The surface, created at the Universitys James Watt Nanofabrication Centre, is covered in tiny pits 120 nanometres across. When stem cells are placed onto the surface, they grow and spread across the pits in a way which ensures they differentiate into therapeutically useful cells.

By covering the PEEK implant in this surface, we can ensure that the mesenchymal stem cells differentiate into the bone cells. This will help the implant site repair itself much more effectively than has ever been possible before and could well mean that implants will last for the rest of patients life.

Dr Dalby added: People are living longer and longer lives nowadays; long enough, in fact, that were outliving the usefulness of some of our body parts. Our new implant could be the solution to the expensive and painful follow-up surgeries which conventional implants require.

Dr Nikolaj Gadegaard, Senior Lecturer in Biomedical Engineering at the University, explained: One of the main selling points of PEEK is that it is very strong, has excellent stability and is very resistant to wear. However, the inertness of the material is not always suitable for implants that require some interaction with the surrounding tissue. Our nanopatterned surface may allow Invibios PEEK polymer to interact with stem cells and enable an effective integration between the implant and the body for the first time.

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Stem cells power implants

In past years, these nine little letters, stem cells, have caused much controversy and misunderstanding.

Stem cells are primitive, undifferentiated cells that are able to divide and become specialized cells of the body such as liver cells, muscle cells, blood cells and other cells with specific functions.

Because they have not yet committed to a developmental path that will form a specific tissue or organ, they are considered master cells with great potential. You may have wondered about what they are used for, and if they hold promise for helping you or a family member with serious disease or injury.

Stem cells are interesting and useful to doctors and scientists for several reasons:

Further work includes potential treatment for Type 1 diabetes, arthritis, stroke, Parkinsons disease, heart disease and Alzheimers disease.

There are also cosmetic applications, using the patients own cells for facial and body enhancement, such as the stem cell facelift, and topical skin applications.

The different types of stem cells include:

These come from embryos that are four to five days old, usually left over from fertility treatments and voluntarily donated.

These were thought to have the most potential for scientific use because they had minimal exposure to potential environmental toxins and great potential for use in tissue and organ regeneration. They are able to self-renew and are pluri-potent, meaning they become any type of cell in the future.

Embryonic cells are also the source of great controversy and debate, since many of us believe that life begins at conception and that manipulation of embryonic stem cells is unethical.

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Positively Beautiful: Ever wondered about stem cells?

A cure for spinal cord injury? Diabetes? Macular degeneration? Hope or just hype? There are now some clinical trials using embryonic stem cells to treat serious diseases for which no other good therapy is currently available. But this is just the beginning of a major medical megatrend that will blossom forth in the coming years. Embryonic stem cells are present after a fertilized egg divides for two or three days. They have the seemingly miraculous ability to turn into any of the tissue types in the bodywhether brain neurons, beating heart cells, bone, or pancreatic islet cells. It is important to understand just where these cells come from. Those used in science are the byproduct of in vitro fertilization (IVF), cells taken from the often left over embryos that are otherwise discarded. In 1998, scientists under the leadership of Dr James Thomson at the University of Wisconsin, learned how to take some of the cells from these about to be discarded embryos and put them into a cell culture basically a fluid in which the cells can grow to produce more cells. These cells in turn can then be directed to grow into heart or lung or pancreas or other types of cells by the addition of various additives to the fluid in which they are growing. So it is from these discards that embryonic stem cells are available to us. Just to be clear. The blastocyst or embryo with its 32 or so cells is not grown in the culture dish. Rather, individual cells are removed and allowed to divide and grow. These are the so called embryonic stem cells. But no embryo is growing, just individual cells. It is true that much can be done with adult stem cells as discussed last time but science so far suggests that embryonic stem cells hold promise for much more benefit. It will probably be embryonic stem cells (or perhaps induced pluipotent stem cells see the first in this series) that pave the way for replacing the islet cells of the pancreas with new insulin producing cells to cure diabetes or replace the damaged cells in the brain that are key to Parkinsons disease. Some strongly feel that it is wrong to use cells from embryos. It is important to remember that these are fertilized eggs that were prepared for couples that could not conceive and so had eggs and sperm placed into a dish with special fluids. Experience has shown that success is better if the doctor implants a few embryos into the womans uterus rather than just one. But the doctor may have more than enough embryos and the extras will be discarded if the woman becomes pregnant. I look at it this way. Since the embryos will be destroyed anyway, why not use them for creating stem cells that perhaps many people with diverse diseases might benefit from. It is not dissimilar to transplanting the organs of a person who has died in a car accident rather than burying them in the grave. And the embryo, made up of just a few cells, is disrupted so each cell grows independently. Now the cells can be stimulated to become heart cells, liver cells or whatever and might be useful in treating a disease. It will take some years but there will certainly be major advances down the road in how we can repair, restore or replace damaged tissues or organs. The pace at which we benefit from stem cell therapy will be influenced by factors including cultural attitudes which in turn lead to legislative decisions and legal challanges. The issues revolving around federal funding via the NIH for research on embryonic stem cells reached the federal courts two summers ago and were further addressed by an appellate court in April of 2011. Cohen and Adashi, writing in the New England Journal of Medicine in May, 2011, gave a clear account of the debate in the courts. They concluded with It is difficult to overestimate the vast potential of stem-cell research. We believe we cannot afford to allow ongoing legal ambiguities to compromise this line of scientific pursuit. Quite the contrary, now is the time to pick up the pace with an eye toward realizing the hoped-for translational benefits. With statutory relief deemed unlikely to be provided before the 2012 elections, it appears all but inevitable that the matter of funding of human ESC research will have to be settled in a court of law. Of course that never happened and stem cell research is not high on the publics set of concerns for this years elections but the makeup of the coming Congress after the election could be relevant down the road. Here is an example of how stem cells could be used: islet cells on demand One day, and I believe it will occur within five to ten years, stem cells will be able to be mass grown into islet cells. They will be ready when the patient needs them. Just give them by vein and they will home into where they need to go. And if they are created from the process called nuclear transfer or adult cells reprogrammed from the patient by genes (iPSC) or proteins (piPSC) that I described previously, they probably will not be rejected because they will be developed to not provoke the immune system. But still, whatever process destroyed their own islet cells years before will probably still be functional. So these new cells may be destroyed over time as well, unless some new technology or drugs are developed to prevent this cell destruction by the body. But in the meantime, just come back for a new infusion whenever needed. Sort of like going to the gas station to refill the tank! Islet cells injected into the vein seem to know to go to the liver and live there and do their work. Bone marrow stem cells when injected by vein go to the bone marrow, take up residence and repopulate the marrow of the patient with leukemia who just got very aggressive treatments to eliminate all of his own marrow cells (and hopefully all of the leukemia cells as well.) But would all stem cells know where to go? Or what to do? Would they go to the heart after a heart attack or do they need to be infused directly into the coronary arteries or injected into the heart muscle itself? And stem cells or stem cells prompted to develop into brain cells will they need to be injected directly into those areas of the brain damaged by Parkinsons or Alzheimers diseases? These are but a few of the issues to be resolved with careful research. Here are just a few studies in progress, some in animals, some in humans and many in laboratory settings: iPS cells have been created for multiple different diseases by taking cells from affected patients such as diabetes type I, Lou Gehrigs disease (amyotrophic lateral sclerosis), Gauchers disease and muscular dystrophy. It is hoped that these cells will help explain the disease processes and their origination. In addition, they might prove useful in growing large numbers of mature cells that could in turn be used for drug screening and drug toxicity evaluations. And in this regard, iPSCs and piPSCs matured into cardiac cells are already being used by pharmaceutical companies to test new drugs for side effects. We all know that if we have a tooth pulled, thats it a tooth wont grow back. But an intriguing study has taken the cells of the progenitors of the molars from mouse embryos and grown them in culture for a few days. Meanwhile, a molar or two from multiple adult mice were extracted. Then the stem cells were implanted into that space and within two months the mice had new teeth with normal structure and strength, demonstrating that stem cells in the proper setting can lead to the re-growth of an organ or tissue. Think about the potential in humans to get a real new tooth rather than a prosthetic tooth or a bridge when a diseased or damaged tooth must be extracted. One of the most exciting studies to get underway was a phase 1 trial of stem cells in patients with spinal cord damage. The Geron Company began this FDA-approved trial in late 2010. They took human embryonic stem cells and from them derived oligodendrocyte progenitor cells; in other words, nerve cells. These were injected next to the spinal cord at the level of very recent injury. In extensive animal experiments, these cells were found able to cause the damaged spinal cord cells to remylinate (basically reapply an insulator as with the covering of an electric wire) and to create some type of nerve growth stimulation with remarkable restoration of some or all function. The rats began to move much more normally within just a week or so of the injection. Then came the human trial. It was Phase 1 meaning that it was all about studying if the injected cells would cause any toxicity. It is a good guess that they would not but because they were be used initially in low dosage (relative to what was used in the rats to obtain responses) so it is unlikely any functional improvement would occur. That would be the test in later trials (Phase 2 and 3) with higher cell numbers provided this Phase 1 study proceeded successfully. As it turned out, Geron Corporation ended the study after enrolling just four patients citing lack of adequate funding to continue. This left Advanced Cell Technology, Inc. as the only other American company conducting a study of embryonic stem cells for macular degeneration and for macular dystrophy in the eyes. They use embryonic stem cells to produce retinal epithelial pigment cells to be injected behind the retina in affected patients. Results will be forthcoming. Another very early Phase I study, this one using adult stem cells, is just beginning in Israel for amyotrophic lateral sclerosis (ALS). The patients own bone marrow stem cells will be treated in the laboratory with a proprietary process by BrainStorm Cell Therapeutics and then placed back into patients. So far 12 of 24 patients have been treated with no apparent adverse effects. The final results will be of real interest. As I said at the beginning, there is still much to be learned before stem cells will become routinely utilized for patient care but progress is real and the opportunities are exciting for a major transformation of medical care in the coming years. Here, as with genomics, we see the value and the importance of innovation. Scientists with good ideas taking the steps needed to bring new and until recently almost undreamed of possibilities to transform healthcare clearly a medical megatrend in the making.

Stephen C Schimpff, MD is an internist, professor of medicine and public policy, former CEO of the University of Maryland Medical Center and is chair of the advisory committee for Sanovas, Inc. and senior advisor to Sage Growth Partners. He is the author of The Future of Medicine Megatrends in Healthcare and The Future of Health Care Delivery- Why It Must Change and How It Will Affect You from which this post is partially adapted.

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Medical Megatrends Stem Cells – Part III